Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes

Abstract

Critical Limb Ischemia (CLI) is common but uncommonly diagnosed. Improved recognition and early diagnostic markers for CLI are needed. Therefore, the aim of our study was to identify plasma biomarkers of CLI in patients with type 2 diabetes mellitus (T2DM). In this study, antibody-coated glass slide arrays were used to determine the plasma levels of 274 human cytokines in four matched cases of diabetes with and without CLI. Potential biomarkers were confirmed in an independent cohort by ELISA. After adjusting for confounding risk factors, only plasma level of Siglec-5 remained significantly associated with an increased odds ratio (OR) for diabetes with CLI by binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off points for Siglec-5 was 153.1 ng/ml. After entering Siglec-5, the AUC was 0.99, which was higher than that of confounding risk factors only (AUC = 0.97, P < 0.05). Siglec-5 was expressed in plaques, but not in healthy artery wall in T2DM patients. Elevated plasma Siglec-5 was independently associated with CLI in T2DM. Plasma Siglec-5 levels are implicated as an early diagnostic marker of CLI in T2DM patients and it may become a target for the prevention or treatment of CLI in diabetes.

Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes

“…Following TASC 2007 criteria CLI was defined as pain at rest, and/or ulcer or gangrene due to peripheral artery disease, transcutaneous oximetry at the dorsum of the foot, 30 mmHg, and/or ankle pressure, 70 mmHg, ABI <0.9, and lower extremity arterial stenosis >50% shown in color Doppler ultrasound scans. Patients with ABI ≥0.9 and <1.3 and normal lower extremity arterial pressure were defined as non-CLI [ 3 , 12 ]. For the initial biomarker discovery studies using protein arrays, non-CLI controls were appropriately matched for sex, age (±5 years), and T2DM duration (±5 years) with the group of patients with CLI.…”

“…Clinical information including details of sex, age, diabetes duration, body mass index (BMI), blood pressure, smoking and drinking habits, blood glucose, glycosylated hemoglobin (HbA1c), lipoprotein lipid levels and previous history of hypertension, hyperlipidemia, and coronary artery disease (CAD) was obtained. Hypertension, hyperlipidemia, and CAD were defined as previously reported [ 3 , 12 ].…”

“…This condition impeded blood supply to the extremities and is associated with significant cardiovascular morbidity and mortality [ 1 , 2 ]. Critical limb ischemia (CLI) is the most severe manifestation of PAD and seriously decreases blood flow to the extremities, which increases the risk of foot ulcers, amputation, and vascular death, especially in diabetic patients [ 3 ].…”

“…Currently, the ankle-brachial index (ABI), color Doppler ultrasound scans, and transcutaneous oxygen pressure are used to confirm the diagnosis of CLI [ 11 ]. Previous studies have implicated some serum or plasma proteins, including Siglec-5, cystatin C, haptoglobin, and 14-3-3 protein zeta as potential biomarkers of CLI in diabetes [ 3 , 12 , 13 ]; however, these markers have not been confirmed due to the limited accuracy of the currently available detection technologies. Therefore, specific biomarkers are urgently required as early diagnostic markers of CLI in T2DM patients to reduce the high incidence of amputations.…”

MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients

“…Briefly, T2DM was defined as fasting glucose levels ≥17.0 mmol/L, or a 2-h plasma glucose value ≥ 11.1 mmol/L during an oral glucose tolerance test or glycated hemoglobin levels >6.5%. CLI was diagnosed based on ABI < 0.9 and lower extremity arterial steno is >50% by color Doppler ultrasound examination 35 , 36 . Patients with ABI values equal to or greater than 0.9 and lower than 1.3, and with a normal lower extremity arterial pressure were defined as non-CLI.…”